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Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II

Strack, Martin; Billard, Étienne; Chatenet, David; Lubell, William D (2017). Urotensin core mimics that modulate the biological activity of urotensin-II related peptide but not urotensin-II Bioorganic and Medicinal Chemistry Letters , vol. 27 , nº 15. p. 3412-3416. DOI: 10.1016/j.bmcl.2017.05.088.

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Résumé

A novel approach for the synthesis of head-to-tail cyclic peptides has been developed and used to prepare two mimics of the urotensin II-related peptide (URP) cyclic core. Mimics 1 and 2 (c[Trp-Lys-Tyr-Gly-ψ(triazole)-Gly] and c[Phe-Trp-Lys-Tyr-Gly-ψ(triazole)-Gly]) were respectively prepared using a combination of solid- and solution-phase synthesis. The silyl-based alkyne-modifying (SAM) linker enabled installation of C-terminal alkyne and N-terminal azide moieties onto linear peptide precursors, which underwent head-to-tail copper-catalyzed azide-alkyne cycloaddition (CuAAC) in solution. In an aortic ring contraction assay, neither 1 nor 2 exhibited agonist activity; however, both inhibited selectively URP- but not UII-mediated vasoconstriction. The core phenylalanine residue was shown to be important for enhancing modulatory activity of the urotensinergic system.

Type de document: Article
Mots-clés libres: Allosteric modulator; Head-to-tail cyclization; Peptide mimicry; SAM-linker; Urotensin-II; Urotensin-II related peptide
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 févr. 2019 15:09
Dernière modification: 28 févr. 2019 15:09
URI: http://espace.inrs.ca/id/eprint/6275

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